Pain management pharmacology Flashcards
(38 cards)
What are the steps of the WHO pain ladder
Start with non-opioids (e.g., paracetamol, NSAIDs).
Add weak opioids for mild to moderate pain (e.g., codeine, tramadol).
Introduce strong opioids for moderate to severe pain (e.g., morphine, fentanyl), possibly in combination with non-opioids.
How do NSAID’s work and give an example of them
NSAIDs work by inhibiting the cyclooxygenase (COX) enzymes, which convert arachidonic acid into prostaglandins, leading to inflammation and pain. So ultimately NSAIDS inhibit prostaglandins, which inhibits the primary neuron preventing the ascending pathway. Key points include:
What are the 2 kinds of COX inhibitors
COX 1 and COX 2 inhibitors
How does aspirin differ from other NSAIDs
Aspirin irreversibly inhibits COX, while other NSAIDs are reversible.
What does COX 1 do
COX-1 (physiological COX) occurs in most cells including gastric parietal cells where it aids in producing the stomach coating to protect the stomach from stomach acid. If it is inhibited this can cause gastric ulcer. (Why you are told to eat food with nsaids).
Explain the COX pathway
Membraneous phospholipids are converted to arachadonic acid to phospholipase.
COX enzymes convert arachadnic acid into prostaglandins (which cause pain and inflammation via ascending pathway)) and thromboxane.
What does COX 2 do
COX 2 (pathological) isn’t involved in stomach or kidney. However COX 2 does increase blood pressure
When should selective COXibs not be given to a patient and why
Selective COX 2 inhibitors, reduce the minor healthy inflammation of the blood vessels which can lead to constriction of the blood vessels. This can increase blood pressure and increases risk of angina (constriction of the coronary artery) and myocardial infarction.
When should non selective NSAID’s not be given to a patient and why
f they are non selective they can cause issues. We need COX 1 (physiological) to produce the coating of the stomach, so if it is inhibited that protective coating is inhibited resulting in ulceration.
How do NSAID’s increase the risk of Asthma attack
Nsaids inhibit arachidonic acid from becoming prostaglandins by inhibiting COX enzymes. This shifts the reaction and causes more Leukotriene’s to be produced by lipoxygenase which produces Cystienyl leukotrine resulting in bronchoconstriction.
If a patient has uncontrolled asthma DO NOT GIVE THEM NSAIDS
What is paracetamols mechanism of action
Paracetamol is a weak inhibitor of COX-1 and COX-2, and a weak prostaglandin synthesis inhibitor, primarily acting through the descending serotonergic pathway. It is classified as an analgesic and antipyretic but is not an NSAID. Mechanism not fully understood. Can control mild but not severe pain.
What is the mechanism of action of local anaesthetics and give an example of them
Local anaesthetics (e.g., lidocaine) are weak bases that block sodium channels, preventing action potential propagation. They can be administered topically or intrathecally and are effective in both myelinated and unmyelinated nerves.
Why should local anaesthetics be administered locally or intrathecally and what may happen if it isn’t
They are administered locally as they block sodium channels non selectively which can lead to reducing action potentials by preventing depolarisation in cardiac cells - arryhtmia (BAD!!). They prevent pain by preventing the action potential. If they’re administered at the periphery site they prevent action potential in the primary neurone. If they’re administered at the spinal cord they can prevent action potential in the secondary neurone.
Explain the chemistry of local anaesthetics
They are weak bases and are partially ionised at physiological pH. Unionised forms are ester or amide so membrane permeable. In low concs
What drugs fall under the anticonvulsant class
Benzodiazapines Z drugs Gabapentin and pregabalin
What is the mechanism of action of benzodiazepines
Benzodiazepines always end in Zpam like diazepam and are prescribed for management of anxiety, insomnia and neuropathic pain.
Thet work by enhance GABAergic activity, providing anxiolytic and sedative effects. (mimic descending GABA pathway. Activate GABA A and B receptors and induce chloride influx and potassium efflux which reduces membrane potential which inhibits and delays AP firing and reduces NT release
What do benzodiazepines interact with and what are the dangers associated with it
Benzodiazepines interact with alcohol and can cause respiratory depression and death. Also risk of addiction.
Why would benzodiazepines be given to patients with neuropathic pain in a low or a high dose
Given to patients with neuropathic pain (spinal cord damage so less interneurons so less GABA released) so compensated by giving BZD’s which in low doses enhance the binding of GABA to GABA receptors and in higher doses replace GABA
What is the mechanism of action of Z drugs
act like benzodiazapines but are not chemically benzodiazepines so are named Z drugs they activate GABA A and GABA B receptors which potentiate the potassium channel leading to potassium efflux and chloride influx. Reduces and delays AP firing reducing NT release
What is the mechanism of action of gabapentinoids and pregabalin
By binding to alpha 2 delta VG calcium channels it prevents the influx of calcium and the movement of glutamate out of the presynaptic membrane thus preventing glutamate from binding to DRG causing euphoria relaxation and calmness
Which 3 receptors do opioids exert effect on and what are the side effects if they are binded to and give examples of strong and weak opioids
Mu receptor (μ) - Main target providing analgesia
kappa receptor(κ) - spinal analgesia and hallucination
delta receptor (δ). - peripheral analgesia but proconvulsant. So opioid medicines are designed to target the mu receptor more than the others. But in high doses they will bind to the others causing side effects. Major side effects include: respiratory depression (OIRD), Arrythmia - QT interval prolongation and severe constipation
What is the mechanism of action of opioid receptors
To turn this off, Mu receptors are bound to inhibitory GPCR’s. It switches off adenyl cyclase there is no ATP converter to cAMP resulting in no PKA activation and no calcium influx. At the same time there is neuronal potassium channel activation causing potassium efflux leading to reduced neurotransmission and reduced pain sensation
What areas of the brain do opioids suppress activity in
Pre-Bötzinger complex in the medulla — this area is the pacemaker for breathing rhythm.
Pontine and medullary respiratory centers, which coordinate rate and depth of breathing.
These regions rely on carbon dioxide levels and other signals to trigger breaths.
How do opioids inhibit neuronal activity and cause respiratory depression
Binding to μ-opioid receptors causes:
↓ cAMP
↑ K⁺ efflux (hyperpolarization)
↓ Ca²⁺ influx
Result? Decreased neuronal excitability and suppression of respiratory drive. Normally, rising CO₂ levels trigger increased breathing.
Opioids blunt the brain’s sensitivity to CO₂ → so even dangerously high CO₂ levels don’t trigger increased breathing.
The body simply doesn’t “realize” it needs more oxygen.
